Fungal species are a rich source of bioactive metabolites for agrochemical discovery. LC-MS/MS-guided molecular networking of Aspergillus japonicus led to the isolation of eight rare calbistrin-type polyketides (1-8), including three new derivatives, japonidienes J-L (1-3). Their structures were elucidated by spectroscopic analysis and computational methods. Compounds 1, 2, and 5-8 were evaluated for phytotoxicity against Eleusine indica and Amaranthus retroflexus seeds. Compounds 1 and 2 inhibited E. indica radicle elongation by 89.4% and 87.8%, respectively, comparable to glyphosate, while compounds 1, 2, and 5 inhibited A. retroflexus seedling growth more strongly than glyphosate. Integrated omics, qRT-PCR, and molecular docking/molecular dynamics simulations analyses suggested that compound 1 may affect trehalose-related metabolism through potential interaction with trehalose-6-phosphate synthase. Zebrafish embryo assays indicated relatively low developmental toxicity, supporting calbistrins as promising herbicidal leads.

Chemical investigation of Penicillium ochrochloron YT2022-65, an endophytic fungus obtained from Lonicera japonica, led to the isolation of six structurally diversified ophiobolin derivatives, including a new compound named 16,17-dihydro-ophiobolin X (1) and five known analogues - ophiobolin H (2), (6α)-21,21-O-dihydroophiobolin G (3), (6α)-18,19,21,21-O-tetrahydro-18,19-dihydroxyophiobolin G (4), ophiobolin G (5), and ophiobolin K (6). Their structures were elucidated via integrated HRESIMS and 1D/2D NMR. TDDFT-based ECD calculations established the absolute configuration of 1 as (2S,3R,5S,6S,10S,11R,14R,15S). Cytotoxicity screening revealed that compounds 1, 5, and 6 exhibited moderate activity against A549, HepG2, MCF-7, and THP-1 cell lines, with SAR analysis implicating the C-7 aldehyde group as critical for bioactivity.

One new bisabolane sesquiterpene, 2-bisabolen-1,10,11,12-tetraol (1), along with three known ones, (3R, 6R, 7S, 10S)-1-bisabolen-3,10,11-triol (2), (3R, 6S, 7R)-1,10-bisaboladien-3-ol (3), and nor-bisabolan-1,11-diol (4), were acquired from the extract of Aspergillus taichungensis 299 isolated from the inner tissue of marine red alga Gelidium amansii. Their structures were determined by comprehensive analysis of 1D/2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HRESIMS) data. The antibacterial assay showed that 1 displayed inhibitory activity against the growth of three common pediatric pathogens, Haemophilus influenzae, Streptococcus agalactiae, and Streptococcus pneumoniae, with the MIC values of 16, 8, and 32 mu g/mL, respectively.

Natural sesquiterpenoids possess a variety of skeleton types with intriguing biomedical activities. In this study, a comprehensive chemical study of the endophytic fungus Penicillium oxalicum 2021CDF-3 yielded a new sesquiterpenoid, namely penicivetivane A (1). The chemical structure for 1 was thoroughly ascertained by using HRESIMS and NMR spectroscopic analyses, while the stereochemistry of 1 was further verified by X-ray diffraction analyses. 1 represented a rare natural vetivane-type sesquiterpenoid with a tricyclic 7/5/5 scaffold. Penicivetivane A (1) displayed strong antimicrobial properties against human pathogens Escherichia coli and Staphylococcus aureus, with respective MICs of 4 and 2 μg/mL. This study provided a new vetivane-type sesquiterpenoid with a lead potency for the discovery of anti-infective drugs.

Background:Hepatocellular carcinoma (HCC) is one of the most common solid tumors, resulting in poor survival and high mortality worldwide. MicroRNAs (miRNAs) contained in serum exosomes are being increasing used as targets for disease diagnosis and treatment. However, the role and the diagnostic potential of exosome-transported miRNAs in HCC remain largely underexplored. Therefore, this study aims to identify differentially expressed exosomal miRNAs in the serum of HCC patients and healthy individuals, clarify the biological function of the key miRNAs in HCC progression, and explore its potential as a diagnostic and therapeutic biomarker for HCC. Methods:In this study, the serum-derived exosomes of patients with HCC and healthy individuals were characterized via transmission electron microscopy (TEM), Western blot assay, and nanoparticle tracking analysis (NTA). The serum-derived exosomes were labeled with PKH-67, and the transport to recipient HCC cells was observed with confocal microscopy. Differentially expressed miRNAs (DEmiRs) encapsulated in serum-derived exosomes were screened via miRNA sequencing, the expression of which was verified through quantitative real-time polymerase chain reaction (qRT-PCR). The association between miR-675-3p and clinicopathological features was investigated via the chi-squared test. The gain and loss of function of miR-675-3p in HCC cells were examined through transfection with mimics and inhibitor. Cell Counting Kit-8 (CCK8), colony formation, 5-ethynyl-2'-deoxyuridine (EdU) staining, and Transwell assays were conducted to test the biological effects of overexpressed and inhibited miR-675-3p on HCC cells in vitro. Tumor xenograft models and immunohistochemistry (IHC) were performed to assess the malignant progression of HCC cells with downregulated miR-675-3p in vivo. Results:Uptake of exosomes from patients with HCC promoted the malignant phenotype of recipient cells. miRNA-675-3p within exosomes was confirmed to be upregulated in the serum of patients with HCC as compared with that of healthy donors. The chi-squared test results showed that miRNA-675-3p was associated with poor survival. Overexpression of miRNA-675-3p promoted the proliferation, invasion, and colony formation of HCC cells in vitro, while downregulation of miRNA-675-3p had the opposite biological effects on HCC cells and inhibited tumor growth and malignant progression in vivo. Furthermore, bioinformatics analysis indicated that miRNA-675-3p was involved in certain cellular processes, especially in lipid metabolism and regulation of several signaling pathways such as PI3K/AKT pathways and PPAR pathways. Conclusions:miRNA-675-3p was upregulated in the serum of patients with HCC and exerted an oncogenic role in HCC cells via the targeting of downstream genes. These findings may constitute novel insights into the development of HCC, with miRNA-675-3p potentially serving as a biomarker for the diagnosis and treatment of patients with HCC.

Sesquiterpenoids have obtained widespread concern because of their intriguing molecular architecture and considerable bioactivities. In the present study of chemical diversity of Aspergillus aculeatinus 2022EX723, an endophytic species derived from the marine green algae Enteromorpha prolifera, three sesquiterpenoids including a new germacrane-type sesquiterpenoid asperacunoid A (1) and two sesquiterpenoids (2 and 3) were isolated and identified. With the assistance of spectroscopic analyses (HRESIMS, NMR, and X-ray analyses), the structures as well as the absolute configuration of 1 were successfully elucidated. Cytotoxic assays against A549, HeLa, HXO-Rb44, and MKN-45 cell lines revealed that asperacunoid A (1) was active against HXO-Rb44 and MKN-45 cells, with respective IC50s of 10.9 and 23.8 μM (compared with the positive control doxorubicin with IC50s of 11.2 μM for HXO-Rb44 and 13.3 μM for MKN-45 cells). This study indicated that the new sesquiterpenoid 1 may be served as a lead compound with high pharmacological potentiality.

During the chemical studies on the target fungus Penicillium oxalicum 2021CDF-3, four compounds (1-4) were isolated and characterized from the culture of the solid rice medium. Their chemical structures were definitely determined by using HRESIMS and NMR experiments. Among them, compound 1 was reported as a new vetivane-type sesquiterpenoid bearing a tricyclic 7/5/5 framework. Compounds 1-4 were measured for their cytotoxicities against A549, MCF7, MKN-45, and HCT 116 cells. Compounds 2 and 4 displayed considerable inhibitory activity on the gastric cancer MKN-45 cell with IC50 values of 8.0 +/- 0.5 and 11.9 +/- 0.6 mu M, respectively.

Filamentous fungi belonging to the genus Aspergillus are prodigious producers of alkaloids, particularly prenylated indole alkaloids, that often exhibit structurally diversified skeletons and potent biological activities. In this study, five prenylated indole alkaloids possessing a bicyclo[2.2.2]diazaoctane core ring system, including a novel derivative, namely aspertaichamide A (1), as well as four known compounds, (+)-stephacidin A (2), sclerotiamide (3), (-)-versicolamide B (4), and (+)-versicolamide B (5), were isolated and identified from A. taichungensis 299, an endophytic fungus obtained from the marine red alga Gelidium amansii. The chemical structures of the compounds were elucidated by comprehensive NMR and HRESIMS spectroscopic analyses. In addition to the previously reported prenylated indole alkaloids, aspertaichamide A (1) was characterized as having an unusual ring structure with the fusion of a 3-pyrrolidone dimethylbenzopyran to the bicyclo[2.2.2] diazaoctane moiety, which was rare in these kinds of compounds. The absolute configuration of 1 was determined by TDDFT-ECD calculations. In vitro cytotoxic assays revealed that the novel compound 1 possessed selective cytotoxic activity against five human tumor cell lines (A549, HeLa, HepG2, HCT-116, and AGS), with IC50 values of 1.7-48.5 mu M. Most importantly, compound 1 decreased the viability of AGS cells in a concentrationdependent manner with an IC50 value of 1.7 mu M. Further studies indicated that 1 may induce AGS cells programmed cell death via the apoptotic pathway.

High-fat diet-induced metabolic syndrome (MetS) is closely associated with cardiac dysfunction. Recent research studies have indicated a potential association between MetS and ferroptosis. Furthermore, metformin can alleviate MetS-induced cardiac ferroptosis. Metformin is a classic biguanide anti-diabetic drug that has protective effects on cardiovascular diseases, which extend beyond its indirect glycemic control. This study aimed to assess whether MetS mediates cardiac ferroptosis, thereby causing oxidative stress and mitochondrial dysfunction. The results revealed that metformin can mitigate cardiac reactive oxygen species and mitochondrial damage, thereby preserving cardiac function. Mechanistic analysis revealed that metformin upregulates the expression of cardiac Nrf2. Moreover, Nrf2 downregulation compromises the cardio-protective effects of metformin. In summary, this study indicated that MetS promotes cardiac ferroptosis, and metformin plays a preventive and therapeutic role, partially through modulation of Nrf2 expression.

目的 探讨Bougie管支撑下行腹腔镜Nissen胃底折叠术治疗食管裂孔疝合并胃食管反流病的临床效果.方法 回顾性分析2017 年10 月至2021 年10 月我科手术治疗的70 例食管裂孔疝合并胃食管反流患者的临床资料,按手术方式分为两组,分别行腹腔镜食管裂孔疝修补+Nissen胃底折叠术(Nissen组,35 例)和腹腔镜食管裂孔疝修补+Bougie管支撑下胃底Nissen折叠术(Bougie组,35 例).比较两组患者围术期指标、术后 1 月内并发症发生率及术后半年胃食管反流指标.结果 Bougie组手术时间、术后恢复饮水时间、术后恢复半流质饮食时间及术后住院时间均少于Nissen组,术后第1、2、3 周胸腹部疼痛、腹胀不适发生率及术后1、2、3、4 周吞咽困难发生率均低于Nissen组,差异均有统计学意义(P<0.05),而两组术中出血量、术后拔除引流管时间、术后首次排气时间、术后 1 月内便秘与腹泻发生率比较均无统计学差异(P>0.05).术后 6 月两组患者食管pH值<4 的次数、反流次数、反流时间、食管下段括约肌压力、DeMeester评分、GERD-Q评分均较术前明显改善(P<0.05),而组间上述各项反流指标比较均无统计学差异(P>0.05).结论 Bougie管支撑下行腹腔镜Nissen胃底折叠术治疗食管裂孔疝合并胃食管反流病,可明显减少术后早期并发症的发生,抗反流效果确切,且并不增加手术难度及手术风险,值得临床推广.

目的:探讨中度肥胖患者行腹腔镜袖状胃切除(LSG)联合空肠旁路术(JJB)的减重效果及并发症缓解优势.方法:统计分析2019年1月至2021年11月行减重手术的61例患者的临床资料.采用历史性队列研究,根据手术方式将患者分为两组,其中31例行LSG(LSG组),30例行LSG+JJB(LSG+JJB组).比较两组患者术前与手术资料、术后6个月减重效果及肥胖并发症缓解情况.结果:两组患者性别、年龄、术前体重、BMI、血压、血糖、血脂指标差异无统计学意义(P>0.05);两组术中出血量、术后排气时间、饮水时间、术后呕吐、术后住院时间及并发症发生率差异均无统计学意义(P>0.05),LSG+JJB组手术时间长于LSG组(P<0.05).术后6个月,两组体重、BMI、多余体重减少百分比、总体重减少百分比、空腹血糖、糖化血红蛋白、收缩压/舒张压、贫血、低蛋白、胆囊结石、脱发、维生素D、维生素B12及叶酸缺乏情况差异无统计学意义(P>0.05),LSG+JJB组甘油三酯、胆固醇低于LSG组(P=0.010,P=0.028),腹泻发生率高于LSG组(P=0.020).结论:对于中度肥胖人群,LSG+JJB仅对高脂血症有明显优势,在减重效果、糖尿病及高血压控制方面无明显优势,中度肥胖人群应谨慎选用.

Halometabolites, usually produced in marine environment, are an important group of natural halogenated compounds with rich biological functionality and drugability and thus play a crucial role in pharmaceutical and/or agricultural applications. In the exploration of novel halometabolites from marine microorganisms, the growing number of halogenated compounds makes it necessary to fully present these metabolites with diverse structures and considerable bioactivities. This review particularly focuses on the chemodiversity and bioactivities of halometabolites from marine-derived fungi. As a result, a total of 145 naturally halogenated compounds, including 118 chlorinated, 23 brominated, and four iodinated compounds, were isolated from 17 genera of marine-derived fungi. Interestingly, many of halometabolites, especially for the brominated and iodinated compounds, are generated by the substitution of bromide and iodide ions for the chloride ion in cultivation process. In addition, these compounds possess diverse structural types, which are classified into polyketides (62.7%), phenols (16.6%), alkaloids (14.5%), and terpenoids (6.2%). Their cytotoxic, antibacterial, and anti-inflammatory activities indicate the high potential of these halogenated compounds as lead compounds for drug discovery.

Chemical investigation of the marine-derived fungus Aspergillus flavipes 297 led to the isolation and identification of three drimane-type sesquiterpenoids, asperflavinoid A (1) and (6-strobilactone-B) esters of (E,E)-6,7-dihydroxy-2,4-octadienoic acids (2 and 3). Asperflavinoid A (1) was characterized as unseparated diastereomers and its chemical structure was determined by spectroscopic analysis of NMR and MS data. In the cytotoxic assay, compound 1 showed promising inhibitory effects on HepG2 and MKN-45 cell lines.

Phenolic bisabolane-type sesquiterpenoids (PBS) represent a rare class of natural products with diverse biological activities. In this study, chemical investigations of the fungus Aspergillus flavipes 297 resulted in the isolation and identification of seven PBS, including a pair of new enantiomers (+)-1a and (-)-1b, a new derivative 2, and five previously reported ones 3-7. The chemical structures of the isolated PBS were determined by extensive NMR and HRESIMS spectroscopic analysis. The absolute configurations of the separated enantiomers (+)-1a and (-)-1b were solved by comparison of the experimental ECD spectra with those of the TDDFT-ECD calculated spectra. The new compounds 1 and 2 represent rare cases of PBS bearing a methylsulfinyl group, which was distinct from the commonly-observed PBS structurally. All the isolated compounds 1-7 were evaluated their antimicrobial and cytotoxic activities. As a result, the tested compounds showed selective antimicrobial activity against several pathogenic bacteria and fungi with the MIC (minimum inhibiting concentrations) values ranging from 2 to 64 mu g/mL. Moreover, enantiomers (+)-1a and (-)-1b, together with compound 2, exhibited promising cytotoxicity against MKN-45 and HepG2 cell lines, respectively, indicating that the methylsulfinyl substituent enhanced cytotoxicity to a certain degree.

目的:探讨腹腔镜直肠癌根治术中低位结扎肠系膜下动脉(IMA)联合自然腔道标本提取(NOSE)的临床效果.方法:回顾性分析2017年6月—2018年11月我院57例直肠癌患者临床资料,其中行低位结扎保留左结肠动脉(低位结扎组)19例,NOSE+低位结扎保留左结肠动脉18例(NOSE组),高位结扎不保留左结肠动脉20例(高位结扎组).比较3组患者术中及术后恢复情况.结果:3组患者一般资料比较差异无统计学意义(P>0.05).3组手术时间、术后疼痛评分、住院时间、预防性造瘘比率、切口感染发生比率比较差异有统计学意义(P<0.05);术中出血量、淋巴结转移数目、第3站淋巴结转移数目比较差异无统计学意义(P>0.05).NOSE组术后排气时间最短、术后疼痛评分最低、住院时间最短(P<0.05).结论:腹腔镜直肠癌根治术低位结扎IMA联合NOSE可以减少吻合口漏发生概率,淋巴清扫效果与高位结扎相当,术后疼痛更轻,有临床推广价值.

目的:分析改良经腹腹膜前修补术(transabdominal preperitoneal,TAPP)术对成人腹股沟斜疝治疗的有效性和安全性.方法:回顾分析84例腹股沟斜疝患者的临床资料,其中观察组40例采用改良TAPP术,对照组54例采用传统TAPP术.比较两组间手术时间、中转手术、手术副损伤、术后第1日疼痛评分、术后静脉止痛药使用时间、术后住院时间、术后并发症发生情况.结果:观察组手术时间单侧为57.4±18.27min,双侧为85.9±25.66 min,分别短于对照组的71.55±21.88min和144.30±37.83 min,差异均有统计学意义(P＜0.05).两组均未发生手术副损伤、中转手术和术后复发,两组间术后第1天疼痛数字评分、术后静脉止痛药使用时间、术后住院时间及术后并发症发生率比较,差异均无统计学意义(P＞0.05).结论:改良TAPP术治疗成人腹股沟斜疝缩短了手术时间,其手术疗效及并发症发生风险与传统TAPP术相当,适合临床推广.

The sperm-associated antigen 5 (SPAG5) plays a key role in controlling cellular processes, including cell cycle progression and proliferation. However, the role of SPAG5 in gastric cancer (GC) remains unclear. Herein, our study showed that upregulation of SPAG5 was detected frequently in GC tissues, and was associated with significantly worse survival in patients with GC. Multivariate analyses revealed that high SPAG5 expression was an independent predictive marker for the poor prognosis of GC patients. Further, SPAG5 knockdown notably inhibited the proliferation abilities of GC in vivo and in vitro. Moreover, our results indicate that SPAG5 promotes cell progression by increasing Survivin expression, which has been reported to control the progression of GC. Moreover, our data demonstrate that Survivin is crucial for SPAG5-mediated GC cell progression in vitro and in vivo. Mechanistically, we demonstrated that SPAG5 promotes the progression of GC via enhancing the Wnt/β-catenin/Survivin axis. Collectively, our data suggest that SPAG5 plays a crucial oncogenic role in GC tumorigenesis, and we provide a novel evidence that SPAG5 may be serve as a prognostic and therapeutic target for GC patients.

目的:探讨腹腔镜胃癌根治术安全性及缩短腹腔镜胃癌根治术学习曲线的方法.方法:回顾性分析腹腔镜胃癌根治术37例患者的临床资料,全胃切除术20例,远端胃切除术17例.按胃肠吻合方式统计,毕氏Ⅰ式吻合1例,毕氏Ⅱ式吻合9例,RY吻合27例.结果:37例均手术顺利完成,平均手术时间196.52±51.63 min,术中出血265.50±132.76 mL,清扫淋巴结28.97±7.91个,术后肛门排气时间2.09±0.73天,住院时间10.94±5.49天.结论:腹腔镜胃癌根治术安全、可行,能达到肿瘤根治效果,通过适当的学习和训练可以缩短学习曲线.

目的:分析腹腔镜疝囊高位结扎术治疗小儿腹股沟斜疝的临床效果.方法:采用腹腔镜疝囊高位结扎术(腹腔镜组)87例,传统小切口疝囊高位结扎术(传统手术组)185例,比较两组平均手术时间、下床活动时间、住院时间、住院费用、术后疼痛评分以及术后阴囊血清肿发生率.结果:腹腔镜组平均手术时间25.00±13.66 min,下床活动时间5.14±3.73 d,分别少于传统手术组的33.29±29.97min和18.52±7.83 d,差异均有统计学意义(P<0.05);腹腔镜组住院费用4554.39±1048.67元,高于传统手术组的3422.45±1634.64元,差异有统计学意义(P<0.05);两组住院天数比较,差异无统计学意义(P>0.05);腹腔镜组术后VAS疼痛评分2.82±1.49分,低于传统手术组的4.73±1.76分,差异具有统计学意义(P<0.05);腹腔镜组无阴囊血清肿发生,而传统手术组有13例(7.03％)发生阴囊血清肿,差异具有统计学意义(P<0.05).结论:与传统小切口疝囊高位结扎术相比,腹腔镜疝囊高位结扎术手术创伤小,手术时间短,术后疼痛轻,术后并发症少,有利于发现对侧隐匿疝,具有有良好的应用前景.